Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT⁺-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT⁺-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
Ameloblastoma/metabolism* ; Humans ; B7-H1 Antigen/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Signal Transduction ; Cell Proliferation ; Up-Regulation ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Telomerase/metabolism* ; Jaw Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Animals ; Cell Line, Tumor ; Female ; Male

Objective To evaluate the accuracy of different convolutional neural networks (CNN),representative deep learning models,in the differential diagnosis of ameloblastoma and odontogenic keratocyst,and subsequently compare the diagnosis results between models and oral radiologists. Methods A total of 1000 digital panoramic radiographs were retrospectively collected from the patients with ameloblastoma (500 radiographs) or odontogenic keratocyst (500 radiographs) in the Department of Oral and Maxillofacial Radiology,Peking University School of Stomatology.Eight CNN including ResNet (18,50,101),VGG (16,19),and EfficientNet (b1,b3,b5) were selected to distinguish ameloblastoma from odontogenic keratocyst.Transfer learning was employed to train 800 panoramic radiographs in the training set through 5-fold cross validation,and 200 panoramic radiographs in the test set were used for differential diagnosis.Chi square test was performed for comparing the performance among different CNN.Furthermore,7 oral radiologists (including 2 seniors and 5 juniors) made a diagnosis on the 200 panoramic radiographs in the test set,and the diagnosis results were compared between CNN and oral radiologists. Results The eight neural network models showed the diagnostic accuracy ranging from 82.50% to 87.50%,of which EfficientNet b1 had the highest accuracy of 87.50%.There was no significant difference in the diagnostic accuracy among the CNN models (P=0.998,P=0.905).The average diagnostic accuracy of oral radiologists was (70.30±5.48)%,and there was no statistical difference in the accuracy between senior and junior oral radiologists (P=0.883).The diagnostic accuracy of CNN models was higher than that of oral radiologists (P<0.001). Conclusion Deep learning CNN can realize accurate differential diagnosis between ameloblastoma and odontogenic keratocyst with panoramic radiographs,with higher diagnostic accuracy than oral radiologists.
Humans ; Ameloblastoma/diagnostic imaging* ; Deep Learning ; Diagnosis, Differential ; Radiography, Panoramic ; Retrospective Studies ; Odontogenic Cysts/diagnostic imaging* ; Odontogenic Tumors

Odontogenic tumors are rare lesions with unknown etiopathogenesis. Most of them are benign, but local aggressiveness, infiltrative potential, and high recurrence rate characterize some entities. The MAP-kinase pathway activation can represent a primary critical event in odontogenic tumorigenesis. Especially, the BRAF V600E mutation has been involved in 80-90% of ameloblastic lesions, offering a biological rationale for developing new targeted therapies. The study aims to evaluate the BRAF V600E mutation in odontogenic lesions, comparing three different detection methods and focusing on the Sequenom MassARRAY System. 81 surgical samples of odontogenic lesions were subjected to immunohistochemical analysis, Sanger Sequencing, and Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometry (Sequenom). The BRAF V600E mutation was revealed only in ameloblastoma samples. Moreover, the presence of BRAF V600E was significantly associated with the mandibular site (ρ = 0.627; P value <0.001) and the unicystic histotype (ρ = 0.299, P value <0.001). However, any significant difference of 10-years disease-free survival time was not revealed. Finally, Sequenom showed to be a 100% sensitive and 98.1% specific, suggesting its high-performance diagnostic accuracy. These results suggest the MAP-kinase pathway could contribute to ameloblastic tumorigenesis. Moreover, they could indicate the anatomical specificity of the driving mutations of mandibular ameloblastomas, providing a biological rational for developing new targeted therapies. Finally, the high diagnostic accuracy of Sequenom was confirmed.
Ameloblastoma/pathology* ; Carcinogenesis ; Humans ; Mitogen-Activated Protein Kinases/genetics* ; Mutation ; Odontogenic Tumors/pathology* ; Proto-Oncogene Proteins B-raf/metabolism* ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Objective: To analyse the quality of life of patients receiving repair of bone defect with folded fibula flap after removal of mandibular ameloblastoma. Methods: The case data of 39 patients with ameloblastoma admitted to the First Affiliated Hospital of Zhengzhou University from August 2013 to April 2016 were retrospectively analysed, including 21 males and 18 females, from 18 to 58 years old. 3D printing and digital technology were used in flap preparation before surgery in all patients. The folded fibular flaps were used to repair mandibular defects and the implants were placed between 6-9 months after surgery. The short form-36 health survey questionnaire (SF-36) and the university of Washington quality of life questionnaire (UW-QOL) were applied to evaluate the quality of life of patients before surgery and at 6 months and 24 months after surgery. The higher the score, the better the condition. SPSS 20.0 was adopted for statistical analysis. Results: The SF-36 survey showed that the mean score of body role before surgery (72.4±11.7) was significantly higher than that at 6 months after surgery (39.6±11.1, t=23.580, P<0.05) or that at 24 months after surgery (59.8±6.4, t=8.358, P<0.001). Compared with the preoperative mean scores of Physical Pain (73.0±11.0), General Health (73.4±10.4) and Health Changes (79.2±3.9) before surgery, the mean scores Physical Pain (53.1±7.7), General Health (53.5±7.5) and Health Changes (63.9±11.7) at 6 months after surgery were decreased significantly respectively (t=13.068, 13.756 and 10.880, respectively, all P<0.05), but the mean scores Physical Pain (78.8±14.0), General Health (80.9±12.6) and Health Changes (84.4±4.6) at 24 months after surgery were increased significantly respectively (t=-2.904, -4.027 and -7.586, respectively, all P<0.05), with significant differences in the mean scores of Physical Pain, General Health and Health Changes between 6 and 24 months after surgery (t=-14.241, -16.490, -14.294, respectively, all P<0.001). The UW-QOL survey showed that the mean scores of chewing, language and taste functions decreased at 6 months after surgery (53.1±6.7, 53.0±7.7 and 62.2±9.9, respectively), but improved at 24 months after surgery (67.9±3.9, 63.9±2.9 and 68.4±11.1, respectively), with statistically significant difference (t=-16.765, -11.675 and 2.498, respectively, all P<0.001). Conclusion: The application of folded fibula flaps to repair bone defects after sugery of mandibular ameloblastoma can better meet the needs of language and chewing functions and improve the quality of life of patients.
Adolescent ; Adult ; Ameloblastoma/surgery* ; Bone Transplantation ; Female ; Fibula/surgery* ; Free Tissue Flaps ; Humans ; Male ; Mandible/surgery* ; Mandibular Neoplasms/surgery* ; Middle Aged ; Quality of Life ; Reconstructive Surgical Procedures ; Retrospective Studies ; Young Adult

PURPOSE: This study reviewed the common conditions associated with displacement of inferior alveolar nerve canal. MATERIALS AND METHODS: General search engines and specialized databases including Google Scholar, Pub Med, Pub Med Central, Science Direct, and Scopus were used to find relevant studies by using keywords such as “mandibular canal”, “alveolar canal”, “inferior alveolar nerve canal”, “inferior dental canal”, “inferior mandibular canal” and “displacement”. RESULTS: About 120 articles were found, of which approximately 70 were broadly relevant to the topic. We ultimately included 37 articles that were closely related to the topic of interest. When the data were compiled, the following 8 lesions were found to have a relationship with displacement of mandibular canal: radicular/residual cysts, dentigerous cyst, odontogenic keratocyst, aneurysmal bone cyst, ameloblastoma, central giant cell granuloma, fibrous dysplasis, and cementossifying fibroma. CONCLUSION: When clinicians encounter a lesion associated with displaced mandibular canal, they should first consider these entities in the differential diagnosis. This review would help dentists make more accurate diagnoses and develop better treatment plans according to patients' radiographs.
Ameloblastoma ; Aneurysm ; Bone Cysts ; Dentigerous Cyst ; Dentists ; Diagnosis ; Diagnosis, Differential ; Fibroma ; Granuloma, Giant Cell ; Humans ; Mandibular Nerve ; Odontogenic Cysts ; Odontogenic Tumors ; Search Engine

Ameloblastoma is a benign locally invasive tumor with a high tendency to recur. It is considered rare in the pediatric population, with most cases diagnosed in the third to fifth decades of life. Approximately 80% of ameloblastomas occur in the molar and ramus region of the mandible, while 20% of cases occur in the maxillary posterior region. This report presents a case of plexiform ameloblastoma in an uncommon location in an 8-year-old child. The lesion was initially thought to be a dentigerous cyst, based on its location and radiographic appearance. The clinical and radiographic features, histopathology, and treatment of solid, plexiform, maxillary ameloblastoma are reviewed, with an added emphasis on a literature review of ameloblastoma in children. This report emphasize the importance of long-term follow-up, since recurrence may occur many years after initial tumor removal.
Ameloblastoma ; Child ; Cone-Beam Computed Tomography ; Dentigerous Cyst ; Follow-Up Studies ; Humans ; Mandible ; Maxilla ; Molar ; Recurrence

OBJECTIVE: To retrospectively analyze the clinical and CT imaging features of desmoplastic ameloblastomas (DA) in comparison with other types of ameloblastomas. METHODS: Patients diagnosed with ameloblastoma histopathologically in Peking University School and Hospital of Stomatology from July 2000 to August 2017 were reviewed to analyze the constituent ratios and characteristics of DA. CT imaging features of DA (28 cases) were investigated in comparison with consecutive cases of solid/multicystic and unicystic ameloblastomas. The following imaging perspectives were analyzed: the border, internal structure, three-dimensional shape, tooth, the periodontium, the cortex and the expansion of the tumors. CT values were measured in the region of interest for quantitative analysis. RESULTS: Among the 1 269 cases of ameloblastomas, 50 (3.9%) were DA, which showed predilections for males (74.0%). The average age of DA was about 43.9 years old, which was higher than the other two types. The anterior incisorcanine region (62.0%) and premolar region (30.0%) were most frequently affected. The incidence rate of DA in mandibule was 56.0% (28/50), which was slightly higher than that of maxilla (44.0%). The DA characteristically showed scallop border and honeycomblike or soapbubble internal structure with bone formation on CT. The mean ratios of height to mesiodistal and buccal-lingual to mesio-distal distances were 0.76 and 0.63, which were higher than the other two types. According to the degree of internal bone formation, three subtypes of DA could be observed: densely ossifying type (I), honeycomb/soap bubble type (II) and sparsely ossifying type (III). The means and standard deviations of CT values of DA were significantly higher than those of the other two types, which were (488.8±164.0) HU (type I), (171.7±102.8) HU (type II), (42.1±8.8) HU (type III). CONCLUSION CT is helpful for diagnosis of DA, which shows as solid tumor with varying degrees of internal ossification.
Adult ; Ameloblastoma ; Female ; Humans ; Jaw Neoplasms ; Male ; Maxilla ; Retrospective Studies ; Tomography, X-Ray Computed

Clear cell odontogenic carcinoma (CCOC), a rare tumor in the head and neck region, displays comparable properties with other tumors clinically and pathologically. In consequence, an incorrect diagnosis may be established. A 51-year-old male patient who was admitted to the Department of Oral and Maxillofacial Surgery at Pusan National University Dental Hospital was initially diagnosed with ameloblastoma via incisional biopsy. However, the excised mass of the patient was observed to manifest histopathological characteristics of ameloblastic carcinoma. The lesion was ultimately diagnosed as clear cell odontogenic carcinoma by the Department of Oral Pathology of Pusan National Dental University. Therefore, segmental mandibulectomy and bilateral neck dissection were performed, followed by reconstruction with fibula free flap and reconstruction plate. Concomitant chemotherapy radiotherapy was not necessary. The patient has been followed up, and no recurrence has occurred 6 months after surgery.
Ameloblastoma ; Ameloblasts ; Biopsy ; Busan ; Diagnosis ; Diagnostic Errors ; Drug Therapy ; Fibula ; Free Tissue Flaps ; Head ; Humans ; Male ; Mandibular Osteotomy ; Middle Aged ; Neck ; Neck Dissection ; Pathology, Oral ; Radiotherapy ; Recurrence ; Surgery, Oral

Ameloblastoma is a benign odontogenic epithelial tumor with high recurrence rate and requires extensive resection of the surrounding tissue and reconstruction of defect site. Because of the anatomical limitation of the reconstruction site, prosthetic treatment with implants is the first recommendation. This is a case of prosthetic restoration of the reconstruction site with implant fixed prosthesis in patient who underwent mandibular resection and iliac bone reconstruction due to ameloblastoma. However 14 months after completion of implant prosthesis, adjacent natural tooth erupted unexpectedly, resulting in 1mm infra-occlusion occurred including posterior implant prosthesis and anterior natural teeth. In adults, implant infra-occlusion may occur due to residual growth after placement of the maxillary anterior implant. But this case, hypo-occlusion of molar implant and open bite of anterior natural teeth is occurred due to extrusion of adjacent tooth, is rare. Thus we report the treatment process including orthodontic treatment with intrusion of the posterior tooth, and investigate the causes of sudden, unexpected tooth extrusion.
Adult ; Ameloblastoma ; Humans ; Mandibular Reconstruction ; Molar ; Open Bite ; Orthodontic Extrusion ; Prostheses and Implants ; Recurrence ; Tooth

Ameloblastoma in the tibia is rare. Limb reconstruction after tumor resection is challenging in terms of selection of the operative method. Here, we report a case of radical resection of an ameloblastoma in the mid-distal tibia combined with limb salvage using a three-dimensional (3D)-printed prosthesis replacement, with 1-year follow-up results. After receiving local institutional review board approval, a titanium alloy prosthesis was designed using a computer and manufactured with 3D-printing technology. During the operation, the stem of the prosthesis was inserted closely into the proximal tibial medullary cavity. Then, the metal ankle mortise and the talus were compacted closely. Radiographic results at 1-year follow up showed that the prosthesis was well placed, and no loosening was observed. The Musculoskeletal Tumor Society (MSTS) 93 functional score was 26 points, and the functional recovery percentage was 86.7%. Computer-assisted 3D-printing technology allowed for more volume and structural compatibility of the prosthesis, thereby ensuring a smooth operation and initial prosthetic stabilization. During the follow up, the presence of bone ingrowths on the porous surface of some segments of the prosthesis suggested good outcomes for long-term biological integration between the prosthesis and host bone.
Alloys ; Ameloblastoma ; Ankle ; Ethics Committees, Research ; Extremities ; Follow-Up Studies ; Limb Salvage ; Methods ; Prostheses and Implants ; Talus ; Tibia ; Titanium